Use of pteridinone derivative serving as EGFR inhibitor

Abstract

The present invention relates to a pteridinone derivative serving as an EGFR inhibitor and use thereof. Specifically, the present invention relates to a compound represented by the following formula I, pharmaceutical composition comprising the compound of the following formula I, and use of the compound in preparation of drugs for treating EGFR-mediated diseases or inhibiting EGFR.

The invention claimed is: 
     
       1. A compound of formula I or a pharmaceutical acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein, 
         R 1  is independently selected from the group consisting of substituted or unsubstituted phenyl, and optionally substituted C 3 -C 8  cycloalkyl; 
         A is a divalent radical -A′-; 
         A′ is a benzene ring, or a five- or six-membered nitrogen-containing heterocycle; 
         R 2  is independently selected from the group consisting of C 2 -C 4  alkenyl substituted acylamino and substituted or unsubstituted C 2 -C 4  alkenyl substituted acyl; 
         m is 0; 
         R 7  is independently selected from the group consisting of: 
       
       
         
           
           
               
               
           
         
       
       and
 R 3 , R 4 , R 5  and R 6  are independently selected from the group consisting of H, substituted or unsubstituted C 1 -C 6  alkoxy, and substituted or unsubstituted C 1 -C 6  alkyl; 
 provided that when R 1  is H and m is 0, R 3 , R 4 , R 5  and R 6  are not each H; and 
 when R 1  is H, m is 0, A′ is a benzene ring and R 7  is 
 
       
         
           
           
               
               
           
         
       
       if one of R 3  and R 6  is a methoxy, the other is not H. 
     
     
       2. A compound or a pharmaceutical acceptable salt thereof selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
       3. The compound of  claim 1 , wherein
 R 1  is substituted or unsubstituted phenyl; 
 R 2  is independently C 2 -C 4  alkenyl substituted acylamino, or C 2 -C 4  alkenyl substituted acyl; 
 R 7  is: 
 
       
         
           
           
               
               
           
         
       
       and
 R 3 , R 4 , R 5  and R 6  are independently selected from the group consisting of H, substituted or unsubstituted C 1 -C 3  alkoxy, and substituted or unsubstituted C 1 -C 3  alkyl. 
 
     
     
       4. A compound or a pharmaceutical acceptable salt thereof selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
       5. The compound of  claim 1 , wherein R 3 , R 4 , R 5  and R 6  are independently selected from the group consisting of substituted or unsubstituted C 1 -C 3  alkoxy and substituted or unsubstituted C 1 -C 3  alkyl. 
     
     
       6. The compound of  claim 1 , wherein the substituted phenyl is halogen or C 1-4  alkoxy substituted phenyl. 
     
     
       7. A pharmaceutical composition, comprising the compound or a pharmaceutical acceptable salt thereof of  claim 2  and a pharmaceutically acceptable carrier or excipient. 
     
     
       8. A method for inhibiting EGFR comprising administering to a patient in need thereof an effective amount of the compound of  claim 2 . 
     
     
       9. A method for treating EGFR-mediated diseases comprising administering to a patient in need thereof an effective amount of the compound of  claim 2 . 
     
     
       10. The method of  claim 9 , wherein the EGFR-mediated disease is cancer. 
     
     
       11. The method of  claim 10 , wherein the cancer is selected from the group consisting of non-small cell lung cancer, small cell lung cancer, lung adenocarcinoma, lung squamous cell carcinoma, breast cancer, prostate cancer, glioblastoma, ovarian cancer, squamous cell carcinoma of head and neck, cervical cancer, esophageal cancer, liver cancer, kidney cancer, pancreas cancer, colon cancer, skin cancer, leukemia, lymphoma, stomach cancer, multiple myeloma, and solid tumors.